An evaluation of serological methods to diagnose tick-borne encephalitis from serum and cerebrospinal fluid

Reusken, Chantal; Boonstra, Marrit B; Rugebregt, Sharona; Scherbeijn, Sandra; Chandler, Felicity; Avšič–Županc, Tatjana; Vapalahti, Olli; Koopmans, Marion; GeurtsvanKessel, Corine H.

doi:10.1016/j.jcv.2019.09.009

Cited by 32 publications

(27 citation statements)

References 38 publications

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“…The evaluation of serum antibodies to TBEV was performed using a commercial ELISA diagnostic assay (Enzygnost ® Anti-TBE Virus (IgM, IgG) test; SiemensGmbH). While concordant results were achieved using the different tests in a separate study [19], a recent report which directly compared four commercial IgG ELISAs revealed pronounced discrepancies, predominantly in the detection of antibodies after vaccination [20]. Although in the present study patients with TBE who were previously vaccinated against this disease were excluded, the limitation is that we did not consider other assays.…”

Section: Discussionmentioning

confidence: 47%

Low Virus-Specific IgG Antibodies in Adverse Clinical Course and Outcome of Tick-Borne Encephalitis

et al. 2021

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Tick-borne encephalitis (TBE) is associated with a range of disease severity. The reasons for this heterogeneity are not clear. Levels of serum IgG antibodies to TBE virus (TBEV) were determined in 691 adult patients during the meningoencephalitic phase of TBE and correlated with detailed clinical and laboratory parameters during acute illness and with the presence of post-encephalitic syndrome (PES) 2–7 years after TBE. Specific IgG antibody levels ranged from below cut-off value (in 32/691 patients, 4.6%), to 896 U/mL (median = 37.3 U/mL). Patients with meningoencephalomyelitis were more often seronegative (24.3%; 9/37) than those with meningoencephalitis (4.7%; 20/428) or meningitis (1.3%; 3/226). Moreover, patients with antibody levels below cut-off had longer hospitalization (13 versus 8 days); more often required intensive care unit treatment (22% versus 8%) and artificial ventilation (71% versus 21%); and had a higher fatality rate (3/32; 9.4% versus 1/659; 0.2%) than seropositive patients. These results were confirmed when antibody levels, rather than cut-off values, were correlated with clinical parameters including the likelihood to develop PES. Low serum IgG antibody responses against TBEV at the onset of neurologic involvement are associated with a more difficult clinical course and unfavorable long-term outcome of TBE, providing a diagnostic and clinical challenge for physicians.

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Section: Discussionmentioning

confidence: 47%

Low Virus-Specific IgG Antibodies in Adverse Clinical Course and Outcome of Tick-Borne Encephalitis

et al. 2021

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“…The production and presence of specific IgM antibodies, usually lasting up to six months, is characteristic of the acute phase of the disease. Specific IgG antibodies persist for years and prove the obtained resistance to TBEV [6,7]. Furthermore, it is well known that human immunoglobulins consist of four polypeptide chains: two heavy and two light chains kappa (κ) or lambda (λ).…”

Section: Introductionmentioning

confidence: 99%

Free Immunoglobulin Light Chains in Patients with Tick-Borne Encephalitis: Before and after Treatment

Gudowska-Sawczuk

Czupryna

Moniuszko

et al. 2021

JCM

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Background: Tick-borne encephalitis (TBE) is inflammation of the central nervous system (CNS) caused by a viral infection which may be associated with increased synthesis of immunoglobulins. It can lead to inter alia, breakdown of the blood-brain barrier (BBB), or even death and, unfortunately, treatment is only symptomatic. Therefore, the aim of the present study was assessment of the concentrations of free light chains (FLC) kappa (κ) and lambda (λ in the cerebrospinal fluid (CSF) and serum of patients with TBE. Methods: A total of 58 cerebrospinal fluid and serum sample pairs were analyzed. Samples were collected from patients with TBE before and after treatment. FLC were measured using the turbidimetric method. The values of κIgG-index, λIgG-index, κFLC-index and λFLC-index were calculated using relevant formulas. Results: Pre-treatment serum λFLC concentrations were higher in comparison to post-treatment levels. Moreover, it was observed that CSF λFLC, TBEV IgM, TBEV IgG, and serum TBEV IgG, as well as the values of λFLC-index, κFLC-index, and λIgG-index were elevated after treatment. In the total study group, the concentrations of CSF κFLC and λFLC, and values of four indexes: κFLC-index, λFLC-index, κIgG-index, and λIgG-index correlated with each other and with CSF TBEV IgM and IgG antibodies. The CSF level of TBEV IgG was also associated with serum IgG TBEV and CSF IgM TBEV antibodies. Additionally, serum κFLC correlated with serum and CSF λFLC. Conclusion: This is the first study that demonstrates statistically significant differences in serum and CSF λFLC, as well as in the calculated values of three algorithms: λIgG-index, κFLC-index, and λIgG-index prior to and following treatment of TBE. Our findings may indicate that these differences reflect the intrathecal synthesis of immunoglobulins and increased permeability of BBB in patients with TBE. Moreover, it could provide the basis for developing new therapeutic strategies.

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“…DENV, YFV, JEV, ZIKV), are due to high level of cross-reactive epitopes among the flaviviruses: (i) cross-reactions by antibodies induced by infection by another flavivirus, (ii) cross-reactive antibodies induced by vaccination against another flavivirus, and (iii) less specific viral antigens used in the assay. Several commercial TBE IgM assays are available and some comparisons between these assays are available at present [27,[37][38][39]. In this study, we compared the ReaScan TBE IgM rapid test with the conventional routine methods of several laboratories in a clinical laboratory setting.…”

Section: Discussionmentioning

confidence: 99%

“…Serum samples from Slovenian patients, which previously tested TBE IgM positive (n = 8) and TBE IgM negative (n = 31) by Enzygnost Anti-TBE virus ELISA IgM test (Siemens GmbH, Marburg, Germany) were analysed [27], which were TBE IgM positive, as well as 68 control potentially cross-reactive serum samples confirmed negative by virus neutralisation test were analysed. The 68 control samples were positive for chikungunya virus (CHIKV; n = 10), CMV (n = 8), DENV (n = 16), EBV (n = 9), JEV (n = 1), ZIKV (n = 10), or from JEV vaccinated (n = 4) or YFV vaccinated patients (n = 10).…”

Section: Institute Of Microbiology and Immunology Ljubljana Sloveniamentioning

confidence: 99%

Multi-laboratory evaluation of ReaScan TBE IgM rapid test, 2016 to 2017

et al. 2020

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Background: Tick-borne encephalitis (TBE) is a potentially severe neurological disease caused by TBE virus (TBEV). In Europe and Asia, TBEV infection has become a growing public health concern and requires fast and specific detection. Aim: In this observational study, we evaluated a rapid TBE IgM test, ReaScan TBE, for usage in a clinical laboratory setting. Methods: Patient sera found negative or positive for TBEV by serological and/or molecular methods in diagnostic laboratories of five European countries endemic for TBEV (Estonia, Finland, Slovenia, the Netherlands and Sweden) were used to assess the sensitivity and specificity of the test. The patients' diagnoses were based on other commercial or quality assured in-house assays, i.e. each laboratory's conventional routine methods. For specificity analysis, serum samples from patients with infections known to cause problems in serology were employed. These samples tested positive for e.g. Epstein-Barr virus, cytomegalovirus and Anaplasma phagocytophilum, or for flaviviruses other than TBEV, i.e. dengue, Japanese encephalitis, West Nile and Zika viruses. Samples from individuals vaccinated against flaviviruses other than TBEV were also included. Altogether, 172 serum samples from patients with acute TBE and 306 TBE IgM negative samples were analysed. Results: Compared with each laboratory's conventional methods, the tested assay had similar sensitivity and specificity (99.4% and 97.7%, respectively). Samples containing potentially interfering antibodies did not cause specificity problems. Conclusion: Regarding diagnosis of acute TBEV infections, ReaScan TBE offers rapid and convenient complementary IgM detection. If used as a stand-alone, it can provide preliminary results in a laboratory or point of care setting.

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An evaluation of serological methods to diagnose tick-borne encephalitis from serum and cerebrospinal fluid

Cited by 32 publications

References 38 publications

Low Virus-Specific IgG Antibodies in Adverse Clinical Course and Outcome of Tick-Borne Encephalitis

Low Virus-Specific IgG Antibodies in Adverse Clinical Course and Outcome of Tick-Borne Encephalitis

Free Immunoglobulin Light Chains in Patients with Tick-Borne Encephalitis: Before and after Treatment

Multi-laboratory evaluation of ReaScan TBE IgM rapid test, 2016 to 2017

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